M THOMAS1, P H FRANCA GOIS2, B E BUTCHER3,4, M TA5, G VAN WYK5,6
1Department of Nephrology, Royal Perth Hospital, Perth, Australia, 2Department of Nephrology, Royal Brisbane And Women’s Hospital, Brisbane, Australia, 3WriteSource Medical Pty Ltd, Lane Cove, Australia, 4University of New South Wales, Sydney, Australia, 5Otsuka Australia Pharmaceutical Pty Ltd, Chatswood, Australia, 6AIH Consulting Pty Ltd, Westleigh, Australia
Aim: Data on real-world all-cause discontinuation of tolvaptan in patients with ADPKD are limited. This retrospective, secondary data analysis investigated all-cause discontinuation of tolvaptan in Australian patients.
Background: Tolvaptan is the only available disease-modifying treatment for ADPKD. Access to tolvaptan in Australia is restricted by a controlled monitoring and distribution program focused on hepatic safety, IMADJIN®.
Methods: Data for all patients initiated on tolvaptan from 17/09/2018 to 29/07/2020, extracted from the IMADJIN® dataset, included age, sex, state of residence, location remoteness, dates of tolvaptan initiation and permanent discontinuation date and reason. Treatment persistence was analysed using Kaplan-Meier methods. Differences in treatment persistence based on age, sex and location were analysed using Cox’s proportional hazard models. Other analyses were descriptive. Missing data were not imputed. (HREC approval RGS0000003858)
Results: 455 patients were included: mean age 50.7±11.4 years, mostly male (57%), from Victoria (30%), NSW (26%) or Queensland (26%), mostly living in a major city (68%). After median follow-up of 9.6 months (95%CI 1.3, 19.9), the K-M estimate of 12-month persistence was 76% (95%CI 71%, 78%). Overall, 22% (n=102/455) discontinued. Age, sex, state and remoteness did not significantly affect treatment persistence. 2.0% discontinued due to hepatic adverse events (abnormal ALT, AST and/or bilirubin). Other clinically important reasons for discontinuation included aquaretic tolerability (4.2%), disease progression (1.1%), and acute renal impairment (0.2%). One patient died during follow-up (cause reported as lung cancer; unrelated to tolvaptan treatment).
Conclusions: Persistence to tolvaptan within the IMADJIN® dataset was comparable to pivotal trials of tolvaptan and to real-world persistence rates to other medications used in chronic kidney disease (e.g. anti-hypertensives). Discontinuation due to hepatic adverse events was low. Study funded by Otsuka.
Pedro Franca Gois attended medical school at the Ruprecht-Karls-Universitaet in Heidelberg, Germany (2001-2004). He started his research career at the German Cancer Centre in a laboratory headed by Prof zur Hausen (Nobel prize in 2008). Pedro completed his internship in Brazil and subsequently trained in Internal Medicine, ICU and Nephrology. Pedro obtained his PhD and post-doc at the University of Sao Paulo, Brazil, granted by FAPESP. He also completed a 2-year Fellowship in Nephrology at the RBWH. Pedro is currently a Consultant Nephrologist at the RBWH and conducts research in Internal Medicine and Nephrology.